5-Year Follow-up of KEYNOTE-042: Pembrolizumab Versus Chemotherapy in NSCLC

By: Victoria Kuhr, BA
Posted: Wednesday, January 18, 2023

After 5 years of follow-up in the phase III KEYNOTE-042 study, first-line pembrolizumab monotherapy continued to show greater clinical benefits than chemotherapy in patients with PD-L1–positive, locally advanced or metastatic non–small-cell lung cancer (NSCLC) without EGFR or ALK alterations. Additionally, Gilberto de Castro, Jr, MD, PhD, of the Instituto do Câncer do Estado de São Paulo, Brazil, and colleagues reported that longer-term follow-up demonstrated that pembrolizumab was associated with fewer treatment-related adverse events than chemotherapy. These findings were published in the Journal of Clinical Oncology.

“More than half of the patients who completed 35 cycles of pembrolizumab were alive 4 years after completing treatment (approximately 6 years after random assignment),” said the study authors. “And a high disease control rate was observed in patients who received a second course of pembrolizumab.”

The study recruited patients with locally advanced or metastatic NSCLC without EGFR or ALK alterations. The patients also had a PD-L1 tumor proportion score (TPS) of more than 1%. All patients received pembrolizumab at 200 mg once every 3 weeks for 35 cycles or chemotherapy (carboplatin plus paclitaxel or pemetrexed) for four to six cycles with optional maintenance pemetrexed. Primary objectives were overall survival in PD-L1 TPS groups greater than 50%, greater than 20%, and greater than 1%.

A total of 1,274 patients were enrolled in the study, in which 637 received pembrolizumab and 637 received chemotherapy. The median follow-up was 61.1 months. The patients treated with pembrolizumab had significantly longer overall survival compared with chemotherapy with PD-L1 TPS groups greater than 50%, 20%, and 1%. The outcomes of overall survival favored pembrolizumab versus chemotherapy regardless of PD-L1 TPS. The estimated 5-year overall survival rates with pembrolizumab were 21.9%, 19.4%, and 16.6% in those with TPS scores greater than 50%, greater than 20%, and greater than 1%, respectively. The objective response rate was 84.3% among 102 patients who completed 35 cycles of pembrolizumab and 15.2% among 33 patients who received second-course pembrolizumab.

Disclosure: For full disclosures of the study authors, visit https://ascopubs.org.

Journal of Clinical Oncology